Prostate cancer remains a significant health concern, with existing treatments often proving invasive or inadequate in preventing recurrence. This study explores the development and preclinical validation of silicon-phthalocyanine (SiPc)-based photosensitizers (PSs) targeted at prostate-specific membrane antigen (PSMA) for photodynamic therapy (PDT). Two PSMA-targeted SiPcs, monovalent and bivalent, were synthesized with axial conjugation through Si-O-C linkages to evaluate their efficacy and specificity. The bivalent SiPc-PQ-(PSMAi)2 demonstrated superior optical properties, reduced aggregation, and enhanced target specificity compared to the monovalent SiPc-PQ-PSMAi. Cellular and in vivo assays confirmed its high PSMA-specific uptake, potent photoinduced cytotoxicity mediated by reactive oxygen species, and significant tumor growth inhibition post-PDT. These findings underscore the potential of bivalent SiPc-PQ-(PSMAi)2 as an effective agent for targeted PDT, combining imaging and therapeutic capabilities for improved prostate cancer management. Further optimization and clinical evaluation could establish its role in theranostic strategies to enhance surgical outcomes and reduce recurrence.

This study focuses on the design and evaluation of a series of A2BC aminoporphyrins, featuring electron-donating substituents like pyrene, carbazole, and phenothiazine to enhance their photophysical and biological performance. Detailed characterization through spectroscopic methods, single-crystal X-ray diffraction, and computational analyses revealed insights into their electronic structure and planarity. Photophysical investigations revealed characteristic Soret and Q bands, along with tunable fluorescence and excited-state lifetimes influenced by the meso substituents. Biological evaluation was conducted using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and fluorescence microscopy to assess the photodynamic therapeutic efficacy against T24 bladder cancer cells. The porphyrins exhibited pronounced photocytotoxicity upon 660 nm light activation, attributed to reactive oxygen species (ROS) generation. Cellular analysis, including acridine orange/ethidium bromide and 4',6-diamidino-2-phenylindole staining, confirmed apoptosis induction through chromatin condensation and nuclear fragmentation. The findings highlight the potential of these porphyrins as effective photosensitizers for photodynamic therapy, demonstrating enhanced stability and ROS generation efficiency.

In recent years, cancer has emerged as a major global health threat, ranking among the top causes of mortality. While treatments such as surgery, immunotherapy, radiation therapy, and chemotherapy remain widely used, photodynamic therapy has been gaining significant interest. Most of the photosensitizing agents employed in clinical settings are derived from tetrapyrrolic frameworks, including porphyrins, chlorins, and phthalocyanines. Although these compounds have demonstrated therapeutic effectiveness, they suffer from critical drawbacks, such as limited solubility in water and inadequate (photo)stability. To address these issues, herein, the formulation of the previously reported and promising photosensitizer tetrakis(4-carboxyphenyl) porphyrin into carbon dots is reported. The carbon dots were found with enhanced aqueous solubility, high (photo)stability, and greater singlet oxygen quantum yield overcoming the limitations of the molecular photosensitizer. While being nontoxic in the dark, the carbon dots induced a phototherapeutic effect in breast cancer cells and multicellular tumor spheroids.

Photodynamic therapy (PDT) is a promising non-invasive treatment for tumors. However, the clinical application of existing PDT nanoplatforms remains limited by their complex preparation processes, lack of targeting specificity, and inefficient generation of reactive oxygen species under hypoxic conditions. To address these challenges, a polyion complex (PIC) nanoparticle (NP) system was designed with enhanced PDT efficacy under hypoxia for tumor-targeted therapy. In this system, methylene blue was conjugated onto hyaluronic acid, which mixed with triphenylphosphine modified polyethylenimine to spontaneously form NPs. The PIC NPs were stable over 24 h in PBS with 100 mM NaCl and 10 % serum protein, attributed to synergistic stabilization through hydrophobic interactions, π-π stacking, and electrostatic forces. Notably, PIC NPs predominantly generated superoxide anions (rather than singlet oxygen) upon laser irradiation, even under hypoxic conditions, suggesting a type I photodynamic mechanism. Finally, PIC NPs showed much stronger cancer killing ability than any of the components both in vitro and in 4 T1 tumor-bearing mice due to the enhanced tumor-targeting capacity and PDT efficiency. Thus, the principle "the whole is greater than the sum of its parts" aptly describes the PIC NP system, making it a promising strategy for effective tumor treatment with PDT.

This study aimed to compare the effects of different laser-activated irrigation (LAI) methods on apical extrusion of indocyanine green (ICG).

In this in vitro study, 40 extracted single-canal premolars were instrumented and randomly assigned to 4 groups (n = 10) of (I) ICG (1 mg/mL) + photon-induced photoacoustic streaming (PIPS) with 2940 nm erbium laser, 20 mJ energy, and 50 µs pulse width for 30 s, (II) ICG + shockwave enhanced emission photoacoustic streaming (SWEEPS) with 2940 nm erbium laser with 20 mJ energy, and 50 µs pulse width (two 25 µs pulse widths) for 30 s, (III) ICG + 810 nm diode laser with 250 mW power for 30 s, and (IV) ICG without activation. Photoluminescence (PL) was used to quantify the ICG volume extruded through the apex, and determine the excitation wavelength of the ICG samples. To calibrate the PL results, one random ICG sample underwent inductively-coupled plasma (ICP) test to quantify the sulfur content of the extruded ICG. Considering the chemical formulation of ICG, the concentration of extruded ICG was calculated accordingly. Data were analyzed by one-way ANOVA (alpha=0.05).

The best spectrum was obtained at 390 nm excitation wavelength with 700 V voltage and slit number=10. The study groups had no significant difference in the concentration of apically extruded ICG (P = 0.611).

The tested LAI protocols had no significant difference with each other or with the no activation protocol regarding the apical extrusion of ICG.

Understanding and exploiting bioelectric signaling pathways and physicochemical properties of materials that interface with living tissues is central to advancing tissue regeneration. In particular, the emerging field of bioelectronics leverages these principles to develop personalized, minimally invasive therapeutic strategies tailored to the dynamic demands of individual patients. By integrating sensing and actuation modules into flexible, biocompatible devices, clinicians can continuously monitor and modulate local electrical microenvironments, thereby guiding regenerative processes without extensive surgical interventions. This review provides a critical examination of how fundamental bioelectric cues and physicochemical considerations drive the design and engineering of next-generation bioelectronic platforms. These platforms not only promote the formation and maturation of new tissues across neural, cardiac, musculoskeletal, skin, and gastrointestinal systems but also precisely align therapies with the unique structural, functional, and electrophysiological characteristics of each tissue type. Collectively, these insights and innovations represent a convergence of biology, electronics, and materials science that holds tremendous promise for enhancing the efficacy, specificity, and long-term stability of regenerative treatments, ushering in a new era of advanced tissue engineering and patient-centered regenerative medicine.

Light serves as an excellent external stimulus due to its high spatial and temporal resolution. The use of light to regulate biological processes has evolved into a vibrant field over the past decade. Employing light on chemical substances such as bioactive molecules and drug delivery systems offers a promising therapeutic approach to achieve precise control over biological processes. In this review, we provide an overview of the advancements in optochemical technologies for controlling bioactive molecules (photopharmacology) and drug delivery systems (photoresponsive drug delivery), with an emphasis on their relationship and biomedical applications. Gaining a deeper understanding of the underlying mechanisms and emerging research will facilitate the development of optochemically controlled bioactive molecules and photoresponsive drug delivery systems, further enhancing light technologies in biomedical applications.

Photoimmunotherapy has emerged as a promising strategy for cancer therapy due to its increased therapeutic effect, ability to reverse drug resistance, and enhanced immune activation. But there is still a lack of effective nanomaterial-based photothermal therapy (PTT) or photodynamic therapy (PDT) agents in photoimmunotherapy. In this study, photosensitizer hematoporphyrin-modified G5 PAMAM (G5-HP) nanomaterials are synthesized, which exhibit excellent photothermal conversion capability and photodynamic effects under 660 nm irradiation, effectively inducing tumor cell ablation and immunogenic cell death (ICD). Besides, ICD induced by G5-HP can generate tumor-associated antigens, thereby enhancing dendritic cell (DC) maturation and subsequent T cell activation. In addition, G5-HP polymers can bind to Toll-like receptor (TLR) agonists CpG-ODN through electrostatic interaction, forming stable G5-HP/CpG nanoparticles. The incorporation of CpG-ODN as an immunoadjuvant further amplified DC maturation, synergizing with phototherapy to strengthen antitumor immunity. Notably, in vivo studies confirmed that G5-HP/CpG nanoparticles significantly suppressed colorectal tumor growth under laser irradiation, while maintaining excellent biocompatibility. Taken together, the synthesized G5-HP polymers perform excellent PTT and PDT efficacy, and the formed G5-HP/CpG nanoparticles effectively integrate phototherapy with DC-mediated immunotherapy. This study offers a promising strategy for colorectal cancer treatment, leveraging the synergistic effects of phototherapy and immunotherapy to achieve superior antitumor outcomes.

In situ vaccination (ISV) has emerged as a promising strategy in cancer immunotherapy, offering a targeted approach that uses the tumor microenvironment (TME) to stimulate an immune response directly at the tumor site. This method minimizes systemic exposure while maintaining therapeutic efficacy and enhancing safety. Recent advances in nanotechnology have enabled new approaches to ISV by utilizing nanomaterials with unique properties, including enhanced permeability, retention, and controlled drug release. ISV employing nanomaterials can induce immunogenic cell death and reverse the immunosuppressive and hypoxic TME, thereby converting a "cold" tumor into a "hot" tumor and facilitating a more robust immune response. This review examines the mechanisms through which nanomaterials-based ISV enhances anti-tumor immunity, summarizes clinical applications of these strategies, and evaluates its capacity to serve as a neoadjuvant therapy for eliminating micrometastases in early-stage cancer patients. Challenges associated with the clinical translation of nanomaterials-based ISV, including nanomaterial metabolism, optimization of treatment protocols, and integration with other therapies such as radiotherapy, chemotherapy, and photothermal therapy, are also discussed. Advances in nanotechnology and immunotherapy continue to expand the possible applications of ISV, potentially leading to improved outcomes across a broad range of cancer types.

Pressure-sensitive paints (PSPs) are an optical surface pressure sensor for aerodynamic measurements that operates through the oxygen dependent luminescence of a luminophore molecule. The luminophore has remained relatively consistent over the past 20 years, with platinum(ii)/palladium(ii)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorphenyl)-porphyrin (Pt/PdTFPP) being popular choices due to their well-known photostability. In this work, NIR-emitting Pt(ii) and Pd(ii) complexes of tetraphenyl tetrabenzoporphyrins and new para CF3 substituted tetraphenyl tetrabenzoporphyrins have been investigated as improved luminophores in PSP formulations for the first time. The red shifted NIR emission spectra of the benzoporphyrins offer a wider and more conveniently placed spectral window than Pt/PdTFPP, creating more of a spectral gap for a secondary temperature-sensitive luminophore to be used in future binary PSPs. The para CF3 substituted Pt(ii) and Pd(ii) benzoporphyrins exhibited substantially increased luminescent brightness over PtTFPP and PdTFPP (5× higher), resulting in signficantly brighter PSP formulations. The benzoporphyrins greatly improved the performance of polystyrene based-PSPs, increasing pressure sensitivity by 20% and decreasing temperature sensitivity by 50%, compared to the current gold standard PtTFPP and PdTFPP.

Photodynamic therapy (PDT) is a promising strategy for cancer treatment. However, the poor hydrophilicity of most photosensitizers makes them difficult to enter the cells and also susceptible to aggregation-induced quenching in aqueous environment. In this study, we encapsulated protoporphyrin IX (PPIX) by nanostructured lipid carrier to obtain a water-soluble PPIX delivery system (NLC-PPIX). The nanoparticles exhibited high colloidal stability and good fluorescence emission. The generation of 1O2 from the NLC-PPIX was verified using 9,10-anthracenediyl-bis(methylene)dicarboxylic acid (ABDA) as 1O2 indicator. The 1O2 quantum yield of the NLC-PPIX in aqueous solution was calculated to be ∼9%. The flow cytometry and fluorescence imaging confirmed the uptake of NLC-PPIX by the A2058 cells and the generation of 1O2 inside the cells under light excitation. The in vitro cytotoxicity assay showed that the NLC-PPIX exerted no toxicity on the A2058 cells under dark conditions, while light irradiation triggered high phototoxicity. The cell viability of the A2058 cells was significantly decreased and the inhibition rate reached approximately 96% by treating the cells with 200 μg/mL NLC-PPIX and 420 nm light irradiation. The successful cancer cell uptake and PDT effect revealed the therapeutic promise of our drug delivery system.

Hypericin from St. John's wort has been used as a potent photosensitizer, but its working mechanism remains elusive which hinders its rational design for improved functionality. We implement ultrafast spectroscopy and quantum calculations to track the excited-state dynamics in an intricate hydrogen-bonding network of hypericin in solution. Using femtosecond transient absorption (fs-TA), we track excited state intramolecular proton transfer (ESIPT) via a previously unreported blueshift of a long-wavelength stimulated emission (SE) band with excitation-dependent dynamics in various solvents, owing to the dominant Q7,14 tautomer that undergoes bidirectional ESIPT. This finding is corroborated by ground-state femtosecond stimulated Raman spectroscopy (GS-FSRS) and density functional theory (DFT) calculations. Moreover, contrasting the neutral and anionic forms of hypericin enables us to reveal an intramolecular charge transfer step underlying ESIPT. We demonstrate UV and visible excitations as an integral platform to provide direct insights into the photophysics and origin for phototoxicity of hypericin. Such mechanistic insights into the excited state of hypericin will power its future development and use.

Photodynamic therapy has garnered significant attention over the past decades for its potential in treating various types of cancer, as well as bacterial, fungal, and viral infections. However, current clinically approved photosensitizers based on a tetrapyrrolic scaffold face notable limitations, including low water solubility, slow body clearance, and photobleaching. As a promising alternative, Ru(II) polypyridyl complexes have emerged due to their favorable photophysical and biological properties (i.e., reactive oxygen species generation, high water solubility, and biocompatibility). Despite these attractive properties, the vast majority of compounds are associated with poor tumor accumulation, representing a major hurdle for therapeutic applications. To overcome this limitation, herein, the chemical synthesis and photophysical evaluation of the functionalization of a Ru(II) polypyridyl complex with an aldehyde group, as a synthetic precursor for further conjugation, is reported. To ensure that the intrinsic chemical reactivity of the aldehyde group remains unaffected by the coordination environment to the metal center, a phenyl spacer was strategically introduced between the central ligand framework and the aldehyde functionality. Computational studies indicated that upon excitation of the metal complex, an excited state electron from the ruthenium t2g orbital is transferred to the π* ligand orbital in a metal-to-ligand charge transfer transition. The compound was found to be highly stable under physiological conditions as well as upon irradiation. Upon light exposure, the metal complex was found to efficiently convert molecular oxygen to singlet oxygen. These findings highlight the potential of the aldehyde functionalized Ru(II) polypyridyl complex as a versatile precursor for photodynamic therapy.

Cerenkov light (CL), utilized as an internal excitation source for photodynamic therapy (PDT), addresses the limitations of laser penetration and has substantial potential for seamlessly integrating clinical radiotheranostics with phototheranostics. Nevertheless, the effectiveness of CL-mediated PDT is significantly hindered by challenges, such as the low intensity of CL and inadequate energy transfer between the CL donor and photosensitizers (PSs). In this study, a novel approach is introduced for enhanced radionuclide-activated radio-photodynamic therapy utilizing a hybrid nanoparticle system composed of lanthanide nanoparticles and an aggregation-induced emission photosensitizer (AIE PS), designated LnNP-TQ NPs. This system enables lanthanide nanoparticles to optimize the decay energy of radionuclides, effectively sensitizing the AIE PS through triplet energy transfer (TET)-mediated processes with an efficiency approaching 100%. When activated by the clinical radionuclide 18F for positron emission tomography imaging, the LnNP-TQ NPs substantially inhibited tumor growth via effective singlet oxygen (1O2) generation. This strategy, which optimally harnesses radionuclide energy and achieves efficient energy transfer, offers a promising pathway for enhancing radiotherapy-phototherapy efficacy in tumor treatment.

Metal coordination compounds are currently a focus of research in developing new photosensitizers for materials and medicinal applications. As an abundant element in the earth's crust aluminum is a suitable target element. However, only limited studies are available on its use in photoactive systems. We now report the facile preparation of a library of homoleptic tris(dipyrrinato)aluminum(III) [AL(DIPY)3] complexes. The majority of complexes was characterized by single crystal X-ray analysis and their photophysical properties upon photoexcitation and their tendency to react with the molecular oxygen of the microenvironment and generate singlet oxygen - in polar and non-polar environment was investigated. These studies are complemented by density functional theory (DFT) calculations to assess the possible electronic distribution on the frontier molecular orbitals within the complexes. As a result of charge transfer states, long-lived triplet excited states were formed and allowed for singlet oxygen generation. An initial screening of the AL(DIPY)3 complexes via in vitro phototoxicity studies against a mouse colon carcinoma cell line (CT26) was promising as these complexes were able to trigger cell death upon irradiation at nanomolar and micromolar concentrations. The results highlight the potential of aluminum dipyrrin complexes as a broadly applicable class of photosensitizers.

Photodynamic therapy (PDT) is a minimally invasive treatment modality that utilizes photosensitizing agents, light, and molecular oxygen to produce cytotoxic reactive oxygen species (ROS) to treat cancerous cells and bacterial infections. However, the effectiveness of PDT is often limited by the penetration depth of the light used to activate the photosensitizer (PS). We propose an effective method to address this challenge using Second Harmonic Generation (SHG), a nonlinear optical process in which two identical photons combine to form a new photon with double the frequency. This technique enables the utilization of longer wavelengths for enhanced tissue penetration, subsequently converting them into shorter wavelengths that align with the absorption characteristics of the photosensitizer. Thus, to achieve a highly effective production of SHG, we successfully synthesized the Harmonic Nanoparticle (HNP), Bismuth Ferrite (BFO). Subsequently, BFO was conjugated with Protoporphyrin IX (PPIX) to get BFO-PPIX conjugates for PDT treatment. These were exposed to Near Infrared (NIR) femtoseconds pulsed laser with a wavelength of 798 nm. PDT experiments using BFO-PPIX conjugates and an 8-minute irradiation by a 798 nm pulse laser reduced the survival rate of cultured Staphylococcus aureus (S. aureus) bacterial cells to 44.5 % ± 3.4 %. To the best of our knowledge, BFO and BFO-PPIX conjugates have not been used previously for advancing the conventional PDT treatment using SHG for deeper and precise treatment in S. aureus.

Cervical esophageal cancer (CEC) is an uncommon malignancy accounting for <5% of all esophageal carcinomas. Treatment of CEC varies and is adapted from established regimens used for squamous cell carcinoma (SCC) or the lower esophageal and head and neck. The present systematic review and guidelines are intended to assist treatment decision making for patients with CEC based on the available evidence.

Using the Population, Intervention, Comparator, Outcome, Timing, and Study Design (PICOTS) framework, the evidence regarding treatment outcomes was assessed using Cochrane and PRISMA 2020 methodology. Eligible studies included prospective Phase II to III trials and retrospective analyses published between January 1, 2013 and February 23, 2024 in the Ovid Medline database. These references were assessed through the American Radium Society (ARS) Appropriate Use Criteria (AUC) methodology. A systematic review PRISMA 2020 checklist confirmed the completion of essential elements. RAND-UCLA consensus methodology was used by the expert panel to rate the appropriateness of the treatment options.

ARS AUC recommendations include (1) larynx preservation using endoscopic resection (EMR or ESD) alone for the typical case with pT1a cN0 cM0 CEC, (2) definitive CRT for the typical case with cT1bN0M0 in patients who cannot undergo endoscopic resection, (3) larynx-preserving using definitive CRT (with or without induction chemotherapy) for the typical case with nonmetastatic locally advanced CEC (advanced T-stage tumors or involved lymph nodes), with surgery reserved for those patients with incomplete response or locoregional recurrence.

This ARS AUC summary provides guidelines for the management of SCC of the cervical esophagus provides based on available evidence. Topics that warrant further investigation include optimization of (1) patient selection; (2) multimodality therapies including chemotherapy, immunotherapy, and targeted agents; (3) radiation dose, schedule, and treatment volume; and (4) supportive care for patients with CEC. Ongoing trials continue to improve outcomes for patients with CEC.

Photodynamic therapy (PDT) is a minimally invasive treatment that utilizes a photosensitizer, specific light wavelengths, and oxygen to generate reactive oxygen species (ROS), causing oxidative damage and tumor cell death. However, the effectiveness of PDT can be reduced by the intrinsic antioxidant and DNA repair mechanisms of tumor cells. Artemis (SNM1C/DCLRE1C) is an endonuclease essential for repairing DNA double-strand breaks (DSBs) via non-homologous end-joining (NHEJ). Herein, we conducted a high-throughput small-molecule screening and identified Punicalagin (PUG), a natural polyphenol from pomegranate, as a novel Artemis inhibitor with an IC50 value of 296.1 nM. We also investigated the effects of PUG combined with PDT in tumor treatment, using the pentalysine β-carbonylphthalocyanine zinc (ZnPc5K) as the photosensitizer. In HeLa cells, ZnPc5K-based PDT induced significant DSBs, which could be repaired by the intrinsic DNA repair mechanisms within 12 h. Co-treatment with PUG compromised DNA repair, promoted cell apoptosis, inhibited cell invasion, and suppressed the growth of various tumor cells. Furthermore, in a mouse xenograft model, the combination of PUG and ZnPc5K-PDT effectively inhibited tumor growth with minimal side effects. These findings suggest that PUG, as an Artemis inhibitor, can enhance the therapeutic efficacy of PDT in tumor suppression by impairing DNA repair through the NHEJ pathway.

The successful diagnosis and treatment of early-stage breast cancer enhances the quality of life of patients. As a promising alternative to recently developed magnetic resonance imaging-guided radiotherapy, we proposed fluorescence molecular imaging-guided photodynamic therapy (FMI-guided PDT), which requires no expensive equipment. In the FMI simulations, ICG-C11 which has emission peaks at near-infrared wavelengths was used as the FMI agent. In the PDT simulation, Upconversion nanoparticles-Quantum dots-Rose bengal (UCQR) which was a PDT agent with upconversion capabilities was used.

The feasibility of breast cancer diagnosis and treatment using our proposed method is evaluated through Monte Carlo simulations of exact light transport through a realistic breast model in the prone position. Monte Carlo modeling in voxelized media was performed. Fluorescence propagation from the tumor and the amount of singlet oxygen produced within the tumor were estimated from the calculated fluence. Next, the effects of tumor diameter and depth from the skin surface on the simulation results were evaluated.

The simulation results showed successful detection of tumors with diameters of 5-9 mm in the 15-25 mm depth region, where tumors are commonly found. Furthermore, simulations have estimated that those tumors can be completely treated by PDT with less than ten light irradiations.

This study suggests that fluorescent molecular imaging-guided photodynamic therapy may be a potential treatment for early-stage breast cancer. Our method would be more suitable than the conventional method for young women who are at higher risk of radiation exposure effects.

This study aims to investigate the effect and mechanism of photodynamic therapy (PDT) combined with cisplatin on human lung adenocarcinoma A549 cells transplanted tumors in nude mice, and to provide a theoretical basis for clinical PDT. Construction of a nude mouse lung cancer transplantation tumor model using the human lung adenocarcinoma A549 cell line, and the mice were randomly divided into four groups: the control group, the cisplatin alone group, the PDT alone group, and the cisplatin combined PDT group. The apoptosis of tumor cells in the four groups was observed and compared by the TUNEL method, and the mRNA expression levels of apoptosis-related genes Bax, caspase-3 and Survivin, as well as the expression levels of the corresponding proteins, were detected by the real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and the protein immunoblotting technique (Western blot) respectively. The results showed that photodynamic force combined with cisplatin was effective in inhibiting tumor growth, and its effect was superior to that of cisplatin or PDT alone. This may be related to the promotion of apoptosis, specifically through the up-regulation of Bax and caspase-3, and the down-regulation of Survivin gene expression, thus inhibiting cell proliferation.

A 2012 review of therapeutic ultrasound was published to educate researchers and physicians on potential applications and concerns for unintended bioeffects (doi: 10.7863/jum.2012.31.4.623). This review serves as an update to the parent article, highlighting advances in therapeutic ultrasound over the past 12 years. In addition to general mechanisms for bioeffects produced by therapeutic ultrasound, current applications, and the pre-clinical and clinical stages are outlined. An overview is provided for image guidance methods to monitor and assess treatment progress. Finally, other topics relevant for the translation of therapeutic ultrasound are discussed, including computational modeling, tissue-mimicking phantoms, and quality assurance protocols.

Phototherapy based on micro light-emitting diodes (µLEDs) has gained enormous attention in the medical field as a patient-friendly therapeutic method due to its advantages of minimal invasiveness, fewer side effects, and versatile device form factors with high stability in biological environment. Effective cosmetic and medical phototherapy depends on deep light penetration, precise irradiation, and simultaneous multi-site stimulation, facilitated by three-dimensional (3D) optoelectronics specifically designed for complex human matters, defined here as 3D µLEDs. This perspective article aims to present the functionalities and strategies of 3D µLEDs for human-centric phototherapy. This study investigates the effectiveness of phototherapy enabled by three key functionalities such as shape morphing, self-adaptation, and multilayered spatiotemporal mapping of 3D µLEDs. Finally, this article provides future insights of 3D µLEDs for human-centric phototherapy applications.

Photodynamic therapy (PDT) has emerged as a promising and evolving modality in cancer treatment leveraging light-sensitive compounds known as photosensitizers to selectively induce cell death in malignant tissues through the generation of reactive oxygen species (ROS). This review delves into the intricate mechanisms of PDT highlighting the pivotal role of photosensitizers and the resultant oxidative stress that damages cancer cells. It explores the versatile applications of PDT across various cancer types alongside the advantages and limitations inherent to this therapy. Recent technological advancements including improved photosensitizers and novel light delivery systems are also discussed. Additionally the review examines the critical role of arachidonic acid (AA) metabolism in cancer progression detailing the cyclooxygenase, lipoxygenase and cytochrome P450 pathways and their contributions to tumor biology. By elucidating the interplay between PDT and AA metabolism the review underscores the potential of targeting AA metabolic pathways to enhance PDT efficacy. Finally it provides clinical and translational perspectives highlighting ongoing research and future directions aimed at optimizing PDT for improved cancer treatment outcomes.

"Living therapeutic carriers" present a promising avenue for cancer research, but it is still challenging to achieve uniform and durable distribution of payloads throughout the solid tumor owing to the tumor microenvironment heterogeneity. Herein, a living drug sprinkle biohybrid (YB1-HCNs) was constructed by hitching acid/enzyme-triggered detachable nanoparticles (HCNs) backpack on the surface of metabolic oligosaccharide-engineered oncolytic bacteria YB1. Along with the process of tumor penetration by bacterial hypoxia navigation, YB1-HCNs responsively and continuously release HCNs, achieving a uniform distribution of loaded agents throughout the tumor. Upon successive irradiation of laser and ultrasound (US), the HCNs can separately generate type II and type I ROS for superior sono-photodynamic therapy (SPDT), which enables HCNs to synergize with YB1 for a satisfactory therapeutic effect in both superficial normoxic and deep hypoxic regions of the tumor. After a single dose, this efficient combination realized 98.3% primary tumor inhibition rate and prolonged survival of mice for 90 days with no recurrence, further inducing a powerful immunological memory effect to completely suppress tumor rechallenge in cured mice. Such a bacterial hybridization vector enables optimization of the spatial distribution of YB1 and HCNs, providing an innovative strategy to maximize therapeutic outcomes and evoke durable antitumor immunity.

Photodynamic therapy (PDT) involves the use of photosensitizers (PSs) that, upon activation by specific wavelengths of light, generate reactive oxygen species (ROS), including singlet oxygen (1O2) and hydroxyl radicals (·OH), within the targeted tissue, typically tumor cells. The generated ROS induces cellular damage, disrupts cellular processes, and ultimately leads to apoptosis or necrosis of the tumor cells. However, the clinical application of PDT is significantly hindered by the limited tissue penetration ability of light. To address this limitation, laser-free self-luminescent photosensitive systems have emerged as potential solutions for achieving deep-tissue PDT and imaging. This review provides a comprehensive analysis of various laser-independent photosensitive systems, with a particular emphasis on those based on resonance energy transfer (RET), chemically induced electron exchange luminescence (CIEEL), and Cherenkov radiation energy transfer (CRET). The aim is to offer a theoretical framework for the development of novel photodynamic systems and to reassess the application potential of certain previously overlooked photosensitizers (PSs).

Various biomarkers such as proteins play key roles in controlling crucial biochemical processes. The critical concentration of the biomarkers is important to maintain a healthy life. In fact, imbalance in concentration or irregular activity of these can lead to various diseases like Cancer, Alzheimer's etc. Therefore, the disease related biomarkers and their timely detection are key to control the illness. In the literature, a few activity-based probes for the detection of such biomarkers are available. As per the requirement an ideal probe should be very specific to recognize the target analyte and that could be achieved by virtue of having a robust structure and stimuli responsive nature. In this regard, several fluorescent probes are of great choice. Although these fluorescent probes face certain challenges such as aggregation caused quenching, which heavily affects the sensitivity and photostability is another major concern for many fluorescent probes. To overcome these challenges aggregation-induced emissive fluorescent probes found to be an excellent alternative. Aggregation induced emissive luminogens (AIEgens) offer higher signal to noise ratios and found to possess better photostability during sensing and imaging. In the present review we have summarized the development of AIEgenic probes for sensing and imaging of disease related biomarkers. We believe this review could be a guide to design efficient AIEgenic probes for the diagnostics development.

Primary human neutrophils are the most abundant human white blood cells and are central for innate immunity. They act as early responders at inflammation sites, guided by chemotactic gradients to find infection or inflammation sites. Neutrophils can undergo both apoptosis as well as NETosis. NETosis is a form of neutrophil cell death that releases chromatin-based extracellular traps (NETs) to capture and neutralize pathogens. Understanding or controlling the balance between these cell-death mechanisms is crucial. In this study, the chemical synthesis and biologic assessment of a ruthenium complex as a light-activated photosensitizer that creates reactive oxygen species (ROS) in primary human neutrophils is reported. The ruthenium complex remains non-toxic in the dark. However, upon exposure to blue light at 450 nm, it exhibits potent cytotoxic effects in both cancerous and non-cancerous cell lines. Interestingly, the metal complex shifts the cell-death mechanism of primary human neutrophils from NETosis to apoptosis. Cells irradiated directly by the light source immediately undergo apoptosis, whereas those further away from the light source perform NETosis at a slower rate. This indicates that high ROS levels trigger apoptosis and lower ROS levels NETosis. The ability to control the type of cell death undergone in primary human neutrophils could have implications in managing acute and chronic infectious diseases.

Upregulation of Cyclooxygenase-2 (COX-2) in a variety of cancer cell lines, a key enzyme of prostaglandin biosynthesis, relative to surrounding normal tissues results in the use of the COX-2 protein as an attractive molecular target for many anticancer therapeutics. This could have a significant implication for selective destruction of cancer cells via the photodynamic therapy effects, leaving the normal tissue intact.

Here, a COX-2-specific NIR photosensitizer (Se-C6-IMC) was synthesized and developed by conjugating a classic anti-inflammatory drug indomethacin (IMC) as an efficient recognition group for COX-2 protein, with benzo[a]phenoselenazine derivative photosensitizer through hexanediamine linker.

In this study, Se-C6-IMC exhibited a strong NIR absorption in the phototherapeutic window, relatively high 1O2 generation (ΦΔ = 0.74 in CH2C2), and an excellent phototoxicity (IC50 = 0.04 µM, 14.4 J/cm2) against MCF-7 cells as compared to COS-7 cells lacking COX-2 protein expression.

Se-C6-IMC showed the highest intracellular localization in Golgi apparatus, making it to more effective for cellular destruction and Golgi targeted therapy. Thus, Se-C6-IMC might hold great promise as a COX-2-specific NIR photosensitizer for improving the PDT efficiency and new Golgi-targeted PDT development in the future.

Esophageal cancer is the eighth most common cancer worldwide and the sixth leading cause of cancer-related deaths. In this study, we propose a novel esophageal stent equipped with a wireless, battery-free, and movable photodynamic therapy (PDT) unit designed to treat esophageal tumors with flexibility, precision, and real-time control. This system integrates a PDT unit and an electrochemical pneumatic soft actuator into a conventional esophageal stent. Each module incorporates a piezoelectric transducer capable of receiving external ultrasound to power the respective module. These transducers selectively respond to different external ultrasound frequencies, enabling independent operation without mutual interference. The therapy module provides a light source for PDT, inducing the production of cytotoxic reactive oxygen species (ROS) in tumor cells and promoting apoptosis. The pneumatic actuator based on electrochemical principles plays a critical role in controlling the position of the PDT light source, enabling the movement of the therapy module up to 200 mm within 15 min. This allows real-time control to maintain the light source near the tumor, ensuring precise and targeted treatment. The system can wirelessly and in real-time control the PDT light source's position via external ultrasound, offering a novel approach for treating esophageal cancer patients according to the need of tumor's progression.

Tuberculosis (TB) is one of the leading causes of death in the world, despite being a preventable and curable disease. Irrespective of tremendous advancements in early detection and treatment, this disease still has high mortality rates. This is due to the development of antibiotic resistance, which significantly reduced the efficacy of antibiotics, rendering them useless against this bacterial infection. This, in turn, causes immune system evasion, antibiotic treatment failures, and recurrence of disease in patients. Regarding this, photodynamic inactivation (PDI) may serve as a useful substitute for antibiotic therapy against drug-resistant mycobacteria. This century-old therapy is already being used in cancer treatment, dentistry, and skeletal and cardiovascular diseases, but it is not yet used in tuberculosis treatment. Researchers have previously used PDI to eradicate other members of the genus Mycobacteria in both in vitro and in vivo settings. This suggests PDI can be explored against M. tuberculosis too. The one limitation associated with PDI is the use of chemical photosensitizers, which are fatal to normal tissues and induce side effects. Recent studies suggest herbal photosensitizers are equally potent as chemically synthesized ones. Therefore, herbal photosensitizers could be used to solve the problem because of their less toxicity to healthy tissues and decreased frequency of side effects. This review emphasizes the importance of herbal photosensitizers and their role as anti-tuberculosis drugs in PDI therapy and also presents five potential herbal photosensitizers-curcumin, quercetin, resveratrol, aloe emodin, and phloretin that could be utilized in the clinical development of PDT-mediated tuberculosis therapies.

Hydroperoxides of unsaturated membrane lipids (LOOHs) are the most abundant non-radical intermediates generated by photodynamic therapy (PDT) of soft tissues such as tumors and have far longer average lifetimes than singlet oxygen or oxygen radicals formed during initial photodynamic action. LOOH-initiated post-irradiation damage to remaining membrane lipids (chain peroxidation) or to membrane-associated proteins remains largely unrecognized. Such after-light processes could occur during clinical oncological PDT, but this is not well-perceived by practitioners of this therapy. In general, the pivotal influence of lipids in tumor responses to PDT needs to be better appreciated. Of related importance is the fact that most malignant tumors have dramatically different lipid metabolism compared with healthy tissues, and this too is often ignored. The response of tumors to PDT appears especially vulnerable to manipulations within the tumor lipid microenvironment. This can be exploited for therapeutic gain with PDT, as exemplified here by the combined treatment with the antitumor lipid edelfosine.

In this perspective, we present and discuss pre-clinical and some clinical studies demonstrating that local photodynamic therapy (PDT) per se is a treatment modality that can induce systemic anti-tumour immunity, however, the anti-tumour efficacy is strongly enhanced when PDT is combined with other treatment modalities, e.g., vaccines or ICI therapy. PDT has been recognized for over 30 years as a modality inducing strong immune effects in treated tumours. More recently, PDT has become perceived as a distinct type of immunogenic antitumor modality with an attractive potential for use as unique form of clinical cancer immunotherapy. It can be argued that PDT-inflicted tumour tissue injury provokes in situ vaccination effect. In the end of this perspective paper, we express our opinion of challenges and future directions in the field of PDT and PDT + immunotherapy.

Three water-soluble Mn(III)-porphyrin complexes with cationic pyridyl side groups bearing COOH- or OH-terminated carbon chains in the meta or para positions have been synthesized as probes for both magnetic resonance imaging (MRI) and photodynamic therapy (PDT). The complexes Mn-1, Mn-2, and Mn-3 are highly water-soluble, and their relaxivities range between 10 and 15 mM-1 s-1, at 20-80 MHz and 298 K, 2-3 times higher than that of commercial Gd(III)-based agents. The complexes containing carboxylate (Mn-2) or alcoholic (Mn-3) side chains in the para position are endowed with higher relaxivities and have also shown efficient photoinduced DNA cleavage and singlet oxygen (1O2) generation. Mn-3 with stronger photoinduced DNA cleavage has also revealed stabilizing and binding activities for G4 DNA, at a similar level as the known G4 binder Mn-TMPyP4. Nevertheless, the G4-binding activity of Mn-3 was nonspecific. Preliminary tests evidenced photocytotoxicity of Mn-3 on HeLa cells without a significant effect in the absence of light. Altogether, these results underline the potential of such water-soluble Mn(III)-porphyrins for the development of multimodal approaches combining MRI and PDT.

Combination therapy, which involves using multiple therapeutic modalities simultaneously or sequentially, has become a cornerstone of modern cancer treatment. Graphene-based nanomaterials (GBNs) have emerged as versatile platforms for drug delivery, gene therapy, and photothermal therapy. These materials enable a synergistic approach, improving the efficacy of treatments while reducing side effects. This review explores the roles of graphene, graphene oxide (GO), and graphene quantum dots (GQDs) in combination therapies and highlights their potential to enhance immunotherapy and targeted cancer therapies. The large surface area and high drug-loading capacity of graphene facilitate the codelivery of multiple therapeutic agents, promoting targeted and sustained release. GQDs, with their unique optical properties, offer real-time imaging capabilities, adding another layer of precision to treatment. However, challenges such as biocompatibility, long-term toxicity, and scalability need to be addressed to ensure clinical safety. Preclinical studies show promising results for GBNs, suggesting their potential to revolutionize cancer treatment through innovative combination therapies.

Gliomas are aggressive intracranial tumors of the central nervous system with a poor prognosis, high risk of recurrence, and low survival rates. Radiation, surgery, and chemotherapy are traditional cancer therapies. It is very challenging to accurately image and differentiate the malignancy grade of gliomas due to their heterogeneous and infiltrating nature and the obstruction of the blood-brain barrier. Imaging plays a crucial role in gliomas which significantly plays an important role in the accuracy of the diagnosis followed by any subsequent surgery or therapy. Other diagnostic methods (such as biopsies or surgery) are often very invasive. Preoperative imaging and intraoperative image-guided surgery perform the most significant safe resection. In recent years, the rapid growth of nanotechnology has opened up new avenues for glioma diagnosis and treatment. For better therapeutic efficacy, developing microenvironment-responsive nanoplatforms, including novel nanotherapeutic platforms of sonodynamic therapy, photodynamic therapy, and photothermal treatments, are employed for improved patient survival and better clinical control outcome. In this review recent advancement of multifunctional nanoplatforms leading toward treatment of glioma is discussed.

This study investigated whether intravenous administration of tumor cells killed by photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) had antitumor effects on distal tumors. Furthermore, a novel extracorporeal blood circulating 5-ALA/PDT system was developed. 5-ALA/PDT- (low or high irradiation) or anticancer drug-treated cells were intravenously administered to rats in a glioma cancer model. CD8+ T cell infiltration into the tumor and expression of calreticulin were examined. The cell-killing effect in the circulating PDT system and protoporphyrin IX (PpIX) accumulation were evaluated. An antitumor effect was observed only with preadministration of low-irradiated 5-ALA/PDT-treated cells and was characterized by the infiltration of CD8+ T cells into the tumor. In low-irradiated cells, several types of cell death were observed, and cell surface calreticulin expression increased over time. A method for the intravenous administration of 5-ALA/PDT-treated cells along with extracorporeal blood circulation was then developed to target hematologic malignancies. Gradually cell death in the circulating PDT system and tumor-specific PpIX accumulation was confirmed using hematopoietic tumor cells. Thus, the extracorporeal blood circulating 5-ALA/PDT system has a direct cell-killing effect and an antitumor effect via induced immune activity and illustrates a new therapeutic strategy for hematologic malignancies.

A series of N,O donor-based mono- and binuclear four-coordinated boron complexes were synthesized. Depending on the substitution and spacer, these complexes exhibit intense blue, green and yellow emission in solution states. Notably, the fluorescence quantum yields (ΦF) and fluorescence decay (lifetime, τ) of mononuclear boron complexes (2 a-2 e) were higher than the binuclear boron complexes (2 f-2 k). The lowest lifetime and quantum yield in binuclear boron complexes were due to intramolecular rotation induced non radiative processes. The disulphide spacer-based boron complexes 2 i-2 k showed aggregation-caused quenching in the THF/H2O mixture whereas no other complexes were ACQ responsive. These complexes show large Stokes shift, one of them i. e. 2 e has the highest Stokes shift of 130 nm. Further, the electrochemical study suggests the presence of two redox incidences. Theoretical studies show close corroboration between the TD-DFT computed and experimentally measured absorption maxima as well as DFT (GIAO) calculated and experimentally measured 11B NMR values. This complements the appropriate selection of the theoretical methods to shed light on the electronic transitions in the mono- and binuclear BF2 complexes.

Background and Objective: Colorectal adenocarcinoma is considered one of the major causes of cancer-related lethality among other type of malignancies. Given the several limitations and adverse outcomes of conventional therapeutic regimens against colorectal cancer, the focus of many investigations has been attributed to the introduction of a novel combined regimen with harmless agents. The purpose of the present study was to investigate the effect of combined doxorubicin (DOX) treatment and photodynamic therapy (PDT) on colorectal adenocarcinoma cells. Material and Methods: HT-29 cells were exposed to different concentrations of DOX, low-level (630 nm) diode laser, and methylene blue (MB) as a photosensitizer substrate separately and a combination of them. The cytotoxic effect of the DOX, laser, MB, and their combination and the IC50 value for each treatment group were calculated by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT). The malondialdehyde (MDA) content as a biomarker of the lipid peroxidation process and liberated lactate dehydrogenase (LDH) enzyme into supernatant was determined. Results: The results of our study evidenced that a combination of photodynamic light (laser plus MB) and DOX caused a significant reduction in the percentage of HT-29 viable cells compared with control and other treatment groups. In addition, this mentioned combination led to a considerable decrease in IC50 of DOX. Increased cell membrane lipid peroxidation and cell destruction processes in the combination therapy group were proven through significant elevation of MDA content and LDH activity in the medium, respectively. Conclusion: The findings of the present study suggested that DOX combined with PDT had a better therapeutic impact on HT-29 colorectal adenocarcinoma cells. Hence, the simultaneous application of PDT along with antineoplastic drugs improves the chemosensitivity of cancerous cells via the disruption of their membrane and triggering death processes that lead to the decrease of chemotherapeutic agents required doses and undesirable effects.

Tumor-targeted, activatable photoimmunotherapy (taPIT) has been shown to selectively destroy tumor in a metastatic mouse model. However, the photoimmunoconjugate (PIC) used for taPIT includes a small fraction of non-covalently associated (free) benzoporphyrin derivative (BPD), which leads to non-specific killing in vitro. Here, we report a new treatment protocol for patient-derived primary tumor cell cultures ultrasensitive to BPD photodynamic therapy (BPD-PDT). Based on free BPD efflux dynamics, the updated in vitro taPIT protocol precludes non-specific BPD-PDT by silencing the effect of free BPD. Following incubation with PIC, incubating cells with PIC-free medium allows time for expulsion of free BPD whereas BPD covalently bound to PIC fragments is retained. Administration of the light dose after the intracellular free BPD drops below the threshold for inducing cell death helps to mitigate non-specific damage. In this study, we tested two primary ovarian tumor cell lines that are intrinsically chemoresistant, yet ultrasensitive to BPD-PDT such that small amounts of free BPD (a few percent of the total BPD dose) lead to potent induction of cell death upon irradiation. The modifications in the protocol suggested here improve in vitro taPIT experiments that lack in vivo mechanisms of free BPD clearance (i.e., lymph and blood flow).

In the treatment of acute myeloid leukemia (AML), conventional therapies can lead to severe side effects and drug resistance. There is a need for alternative treatments that do not cause treatment resistance and have minimal or no side effects. Sonodynamic therapy (SDT), due to its noninvasive, multiple repeatability, localized treatment feature and do not cause treatment resistance, emerges as an alternative treatment option. However, it has not received sufficient attention in the treatment of AML especially acute promyelocytic leukemia (APL). The aim of the study was to investigate the potential differentiation and antileukemic effects of acridine orange (AO)-mediated SDT on HL60 cells.

Cell viability was determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) method in the control, ultrasound, AO concentrations, and ultrasound-exposed AO concentrations groups. Transmission electron microscopy (TEM) was used to determine morphology, and flow cytometry was used to determine apoptosis, DNA cycle, cell volume, mitochondria membrane potential (Δψm), reactive oxygen species (ROS) production, and differentiation markers (CD11b and CD15) expressions. Additionally, toluidine blue staining for semithin sections was used to determine differentiation.

The cytotoxicity of AO-mediated SDT on HL60 cells was significantly higher than other groups, and TEM images showed that it caused various morphological changes typical for apoptosis. Flow cytometry results showed the presence of early apoptosis, subG1 arrest, loss of Δψm, increase of intracellular ROS production, decreased cell volume, and increased expression of CD11b (1.3-fold) antigen and CD15 (1.2-fold) antigen.

Data showed that AO-mediated SDT significantly induced apoptosis in HL60 cells. Increased expression of CD11b and CD15 antigens and morphological findings demonstrated that AO-mediated SDT contributes to granulocytic differentiation in HL60 cells. AO-mediated SDT has potential as an alternative treatment of APL.

Introduction: Photodynamic therapy(PDT)is a minimally invasive technique increasingly used in dentistry for its antimicrobial properties. This research aimed to evaluate the influence of photodynamic therapy (PDT) on the viability of dental pulp stem cells (DPSCs). Methods: In this laboratory-based, experimental study, DPSCs were cultured in Dulbecco's modified Eagle's medium and maintained at 37 °C. The cells were separated into five groups: Toluidine blue (TBO) at concentration of 0.1 mg/mL and 0.5 mg/mL, as well as methylene blue (MB) at concentrations of 0.01 mg/mL and 0.05 mg/mL were added to the wells in groups 1 to 4. The fifth group served as the control group. After 5 minutes of incubation, the experimental groups were irradiated with Fotosan® light-emitting diode (LED) for one minute. Cell viability was assessed after 8, 24, 48, and 72 hours using the methyl thiazolyl tetrazolium (MTT) assay. Results: Time (P<0.000), photosensitizer type/concentration (P<0.0001), and their interaction effect (P<0.000) on cell viability were all significant. Viability in both MB groups was considerably higher than that in the control group at 8 hours (P<0.001). At 24 hours, no significant difference was observed between the experimental groups and the control (P>0.05). At 48 and 72 hours, cell viability in the TBO groups was markedly lower compared to the control group (P<0.01). Conclusion: PDT with MB at the tested concentrations had no adverse effect on DPSCs even in the long- term (48 and 72 hours).

Introduction: With an alarmingly growing number of patients diagnosed with colorectal cancer, adopting innovative anti-cancer approaches has recently garnered great attention. One interesting concept is the co-administration of cytotoxic agents and safer modalities such as photodynamic therapy (PDT), which can subsequently improve therapeutic efficacy and potentially reduce the risks of severe adverse effects and drug resistance. In the course of PDT, a locally injected photosensitizer (PS) is irradiated with a light source, which subsequently generates reactive oxygen species (ROS) and induces programmed cell death in tumor cells. Methods: In this study, to evaluate the potential anti-cancer effects of chemotherapy combined with PDT, in comparison to each alone, we employed PDT, comprising methylene blue (MB) and diode lasers at 630 and 810 nm wavelengths, in conjunction with the chemotherapeutic agent doxorubicin (DOX). Results: The MTT assay showed that the viability of colorectal cancer HT-29 cells decreased significantly following DOX+PDT treatment. Similarly, lactate dehydrogenase (LDH) release and lipid peroxidation rates were substantially higher in DOX+PDT treatment groups. Lastly, the catalase (CAT) assay indicated that the combination reduced the ability of CAT in the detoxification of H2 O2. Conclusion: Our study suggests that MB-mediated PDT combined with chemotherapy might provide a promising avenue to improve therapeutic efficacy and potentially reduce the risk of adverse effects and drug resistance. Without a doubt, further investigations need to delve into the pharmacological advantages and disadvantages of PTD-based combination therapy and optimize its administered doses along with other modalities.

Pancreatic cancer serves as the third leading cause of cancer-associated morbidity and mortality in the United States, with a 5-year survival rate of only 12% with an expected increase in incidence and mortality in the coming years. Pancreatic ductal adenocarcinomas constitute most pancreatic malignancies. Certain genetic syndromes, including Lynch syndrome, hereditary breast and ovarian cancer syndrome, hereditary pancreatitis, familial adenomatous polyposis, Peutz-Jeghers syndrome, familial pancreatic cancer mutation, and ataxia telangiectasia, confer a significantly higher risk. Screening for pancreatic malignancies currently targets patients with germline mutations or those with significant family history. Screening the general population is not currently viable owing to overall low incidence and lack of specific tests. Endoscopic ultrasound (EUS) and its applied advances are increasingly being used for surveillance, diagnosis, and management of pancreatic malignancies and have now become an indispensable tool in their management. For patients with risk factors, EUS in combination with magnetic resonance imaging/magnetic resonance cholangiopancreatography is used for screening. The role of endoscopic modalities has been expanding with the increased utilization of endoscopic retrograde cholangiopancreatography, EUS-directed therapies include EUS-guided fine-needle aspiration and EUS-fine-needle biopsy (FNB). EUS combined with FNB has the highest specificity and sensitivity for detecting pancreatic cancer amongst available modalities. Studies also recognize that artificial intelligence assisted EUS in the early detection of pancreatic cancer. At the same time, surgical resection has been historically considered the only curative treatment for pancreatic cancer, over 80% of patients present with unresectable disease. We also discuss EUS-guided therapies of physicochemicals (radiofrequency ablation, brachytherapy, and intratumor chemotherapy), biological agents (gene therapies and oncolytic viruses), and immunotherapy. We aim to perform a detailed review of the current burden, risk factors, role of screening, diagnosis, and endoscopic advances in the treatment modalities available for pancreatic cancer.